Phenotypic Changes Research Articles

Integrative analyses of convergent adaptation in sympatric extremophile fishes.

The evolution of independent lineages along replicated environmental transitions frequently results in convergent adaptation, yet the degree to which convergence is present across multiple levels of biological organization is often unclear. Additionally, inherent biases associated with shared ancestry and variation in selective regimes across geographic replicates often pose challenges for confidently identifying patterns of convergence. We investigated a system in which three species of poeciliid fishes sympatrically occur in a toxic spring rich in hydrogen sulfide (H2S) and an adjacent nonsulfidic stream to examine patterns of adaptive evolution across levels of biological organization. We found convergence in morphological and physiological traits and genome-wide patterns of gene expression among all three species. In addition, there were shared signatures of selection on genes encoding H2S toxicity targets in the mitochondrial genomes of each species. However, analyses of nuclear genomes revealed neither evidence for substantial genomic islands of divergence around genes involved in H2S toxicity and detoxification nor substantial congruence of strongly differentiated regions across population pairs. These non-convergent, heterogeneous patterns of genomic divergence may indicate that sulfide tolerance is highly polygenic, with shared allele frequency shifts present at many loci with small effects along the genome. Alternatively, H2S tolerance may involve substantial genetic redundancy, with non-convergent, lineage-specific variation at multiple loci along the genome underpinning similar changes in phenotypes and gene expression. Overall, we demonstrate variability in the extent of convergence across organizational levels and highlight the challenges of linking patterns of convergence across scales.

Defining precancer: a grand challenge for the cancer community.

The term 'precancer' typically refers to an early stage of neoplastic development that is distinguishable from normal tissue owing to molecular and phenotypic alterations, resulting in abnormal cells that are at least partially self-sustaining and function outside of normal cellular cues that constrain cell proliferation and survival. Although such cells are often histologically distinct from both the corresponding normal and invasive cancer cells of the same tissue origin, defining precancer remains a challenge for boththe research and clinical communities. Once sufficient molecular and phenotypic changes have occurred in the precancer, the tissue is identified as a 'cancer' by a histopathologist. While even diagnosing cancer can at times be challenging, the determination of invasive cancer is generally less ambiguous and suggests a high likelihood of and potential for metastatic disease. The 'hallmarks of cancer' set out the fundamental organizing principles of malignant transformation but exactly how many of these hallmarks and in what configuration they define precancer has not been clearly and consistently determined. In this Expert Recommendation, we provide a starting point for a conceptual framework for defining precancer, which is based on molecular, pathological, clinical and epidemiological criteria, with the goal of advancing our understanding of the initial changes that occur and opportunities to intervene at the earliest possible time point.

Lemming and Vole Cycles: A New Intrinsic Model.

It is 100 years since the first paper described the multiannual cycles in Arctic rodents and lagomorphs. The mechanisms driving population cycles in animals like lemmings and voles are complex, often attributed to extrinsic factors, such as food availability and quality, pathogens, parasites and/or predators. While extrinsic factors provide insights into population cycles, none fully explain the phenomenon. We propose an underlying innate, intrinsic mechanism, based on epigenetic regulation, that drives population cycles under harsh arctic conditions. We propose that epigenetically driven phenotypic changes associated with sexual development, growth and behaviour accumulate over time in offspring, eventually producing a phase change from rising population density to eventual population collapse. Under this hypothesis, and unlike previous hypotheses, extrinsic factors modify population cycles but would not be primary drivers. The interaction between our intrinsic cycle and extrinsic factors explains established phenomena like delayed-density dependence, whereby population growth is controlled by time-dependent negative feedback. We advocate integrating a century of field research with the latest epigenetic analysis to better understand the drivers of population cycles.

Phenotypic and Transcriptomic Analysis Revealed a Lack of Risk Perception by Native Tadpoles Toward Novel Non-Native Fish.

The introduction of alien species poses a serious threat to native biodiversity, and mountain lake systems in the southwest of China are particularly vulnerable to the introduction of non-native fish. The prey naivety hypothesis states that native species may not be able to recognize novel introduced species due to a lack of common evolutionary background and therefore become easy targets, so the impacts of non-native fish on mountain endemic amphibians need to be urgently assessed. In an ex-situ experiment, we exposed the tadpoles of the Chaochiao Brown Frog (Rana chaochiaoensis), endemic to western China, to kairomones of both native and translocated fish species, and their phenotypic and genetic response patterns were compared. The results revealed significant phenotypic plasticity responses in total length (TOL), tail length (TL), and tail muscle width (TW) of tadpoles induced by native fish kairomone, while tadpoles exposed to translocated fish kairomone exhibited weaker phenotypic changes. At the transcriptional level, the number of differently expressed genes (DEGs) in the native fish treatment was 3.1-fold (liver) and 52.6-fold (tail muscle) higher than in the translocated fish treatment, respectively. There were more unique DEGs in the native fish treatment, primarily enriched in terms and pathways related to stress response, energy metabolism, and muscle development. The study revealed a lack of risk perception by native tadpoles toward novel non-native fish, providing new evidence for the prey naivety hypothesis from both phenotypic and molecular perspectives. Future conservation efforts should prioritize assessing the impacts of non-native fish on alpine and subalpine threatened and narrowly distributed amphibians. Additionally, prevention, early warning, monitoring, and removal of non-native fish should be carried out as soon as possible.

Mycolactone causes destructive Sec61-dependent loss of the endothelial glycocalyx and vessel basement membrane: a new indirect mechanism driving tissue necrosis in Mycobacterium ulcerans infection.

The drivers of tissue necrosis in Mycobacterium ulcerans infection (Buruli ulcer disease) have historically been ascribed solely to the directly cytotoxic action of the diffusible exotoxin, mycolactone. However, its role in the clinically-evident vascular component of disease aetiology remains poorly explained. We have now dissected mycolactone's effects on primary vascular endothelial cells in vitro and in vivo. We show that mycolactone-induced changes in endothelial morphology, adhesion, migration, and permeability are dependent on its action at the Sec61 translocon. Unbiased quantitative proteomics identified a profound effect on proteoglycans, driven by rapid loss of type II transmembrane proteins of the Golgi, including enzymes required for glycosaminoglycan (GAG) synthesis, combined with a reduction in the core proteins themselves. Loss of the glycocalyx is likely to be of particular mechanistic importance, since knockdown of galactosyltransferase II (beta-1,3-galactotransferase 6; B3GALT6), the GAG linker-building enzyme, phenocopied the permeability and phenotypic changes induced by mycolactone. Additionally, mycolactone depleted many secreted basement membrane components and microvascular basement membranes were disrupted in vivo. Remarkably, exogenous addition of laminin-511 reduced endothelial cell rounding, restored cell attachment and reversed the defective migration caused by mycolactone. Hence supplementing mycolactone-depleted extracellular matrix may be a future therapeutic avenue, to improve wound healing rates.

SUN1 inhibits osteogenesis and promotes adipogenesis of human adipose-derived stem cells by regulating α-tubulin and CD36 expression.

Sad and UNC84 domain 1 (SUN1) is a kind of nuclear envelope protein with established involvement in cellular processes, including nuclear motility and meiosis. SUN1 plays an intriguing role in human adipose-derived stem cells (hASCs) differentiation; however, this role remains largely undefined. This study was undertaken to investigate the role of SUN1 in hASCs differentiation, as well as its underlying mechanisms. Employing siRNAs, we selectively downregulated SUN1 and CD36 expression. Microtubules were depolymerized using nocodazole, and PPARγ was activated using rosiglitazone. Western blotting was performed to quantify SUN1, PPARγ, α-tubulin, CD36, OPN, and adiponectin protein expression levels. Alkaline phosphatase and Oil red O staining were used to assess osteogenesis and adipogenesis, respectively. Downregulated SUN1 expression increased osteogenesis and decreased adipogenesis in hASCs, concomitant with upregulated α-tubulin expression and downregulated CD36 expression, alongside reduced nuclear localization of PPARγ. Microtubule depolymerization increased CD36 expression. Rescue experiments indicated that microtubule depolymerization counteracted the downregulated SUN1-induced phenotypic changes. This study demonstrates that SUN1 influences the differentiation of hASCs towards osteogenic and adipogenic lineages, indicating its essential role in cell fate.

Characterization of the Clostridioides difficile 630Δerm putative Pro-Pro endopeptidase CD1597.

Clostridioides difficile is the leading cause of antibiotic-associated infections worldwide. Within the host, C. difficile can transition from a sessile to a motile state by secreting PPEP-1, which releases the cells from the intestinal epithelium by cleaving adhesion proteins. PPEP-1 belongs to the group of Pro-Pro endopeptidases (PPEPs), which are characterized by their unique ability to cleave proline-proline bonds. Interestingly, another putative member of this group, CD1597, is present in C. difficile. Although it possesses a domain similar to other PPEPs, CD1597 displays several distinct features that suggest a markedly different role for this protein. We investigated the proteolytic activity of CD1597 by testing various potential substrates. In addition, we investigated the effect of the absence of CD1597 by generating an insertional mutant of the cd1597 gene. Using the cd1597 mutant, we sought to identify phenotypic changes through a series of in vitro experiments and quantitative proteomic analyses. Furthermore, we aimed to study the localization of this protein using a fluorogenic fusion protein. Despite its similarities to PPEP-1, CD1597 did not show proteolytic activity. In addition, the absence of CD1597 caused an increase in various sporulation proteins during the stationary phase, yet we did not observe any alterations in the sporulation frequency of the cd1597 mutant. Furthermore, a promoter activity assay indicated a very low expression level of cd1597 in vegetative cells, which was independent of the culture medium and growth stage. The low expression was corroborated by our comprehensive proteomic analysis of the whole cell cultures, which failed to identify CD1597. However, an analysis of purified C. difficile spores identified CD1597 as part of the spore proteome. Hence, we predict that the protein is involved in sporulation, although we were unable to define a precise role for CD1597 in C. difficile.

Fuel fumes and foliage: the fate of speciated gasoline VOCs during phytoremediation and their impact on the bacterial phenotype

The capacity of indoor plants including green walls to capture, deposit and remediate individual volatile organic compounds (VOCs) has been well documented. However, in realistic settings, plant systems are exposed to a complex mixture of VOCs from highly varied various emission sources. Gasoline vapour is one of the major sources of these emissions, containing high concentrations of the carcinogens benzene, toluene, ethylbenzene and xylene (BTEX). Using both solid phase micro extraction (SPME) and quick, easy, cheap, effective, rugged and safe (QuEChERS) sampling techniques, we assessed the dynamics of individual speciated gasoline VOC phytoremediation from the air and uptake within green wall plant species and growth substrates within a small passive green wall system, along with quantifying the phenotypic changes within the plant-associated bacterial communities resulting from gasoline exposure. Over 8 hours the green wall system achieved 100% removal of atmospheric benzene, 1,2,3-trimethyl, eicosane and hexadecane, benzene 1,3-diethyl-; 1,3,5 cycloheptatriene,7- ethyl and carbonic acid eicosyl vinyl ester. All plant species tested demonstrated the accumulation 45 petrochemical VOCs (pVOCs) with Spathiphyllum wallisii successfully accumulating the majority of pVOC functional groups after 24 h of gasoline exposure. Within the plants phyllospheric bacterial communities, changes in both cellular complexity and granularity appeared to increase as a result of gasoline exposure, while cell size diminished. This work provides novel findings on the VOC removal processes of botanical systems for realistic and highly toxic VOC profiles.

Population dynamics and reproductive features of the Amazon River prawn Macrobrachium amazonicum (Heller, 1862) in Neotropical reservoirs under drought events

Here, we describe population and reproductive dynamics of four populations of Macrobrachium amazonicum in reservoirs during drought events. Additionally, we analyze possible phenotypic changes in this species promoted by fish predation. Two populations had a large-size phenotype (with large body proportions and morphotypes in males) while a small-size phenotype (with reduced sizes and no morphotypes) was found in the two other populations. Overall, females were larger than males and there were varying sex ratios among the four studied populations. All populations had bimodal or polymodal patterns in their monthly size-class frequency, suggesting a seasonal influence and a potentially great capacity of these populations to adapt to adverse environmental conditions. No major changes were found in the patterns of sex ratio, recruitment, frequency of (larger) male morphotypes and female ovarian development stages during drought events. Macrobrachium amazonicum is a resilient species and undergoes continuous reproduction. Females with immature ovaries were predominant in all populations, performing multiple spawns and exhibiting rapid ovarian development cycles. In males, the initial morphotype (TC - translucent claw) was predominant in populations with a social hierarchy. Males of dominant morphotypes (GC1 and GC2 - green claw 1 and 2) use more energy to carry out and maintain metabolic processes, which could probably one of the explanations why their number in populations are limited. We did not find any clear evidence that fish predation affected phenotypes, suggesting that phenotypic plasticity could be more related to intrinsic factors, which would have to be further investigated.

Establishment of Genetic Transformation System in Lilium pumilum and Functional Analysis of LpNAC6 on Abiotic Stress

Lilium pumilum is widely distributed in northeast Asia. It exhibits strong resistance and possesses high ornamental value. However, it currently lacks an efficient and stable transformation system. Therefore, we aimed to establish an effective genetic transformation system using the Agrobacterium-mediated method for L. pumilum, enabling gene transfer into the plant for gene function research and genetic engineering breeding. Our genetic transformation system achieved a maximum transformation efficiency of 7.25% under specific conditions: a kanamycin (Kana) concentration of 120mg/L, 3 days of pre-cultivation, an A. tumefaciens concentration of 0.7 OD600, an acetosyringone (AS) concentration of 20mg/L, and a 15-minute infection period. We investigated the function of the LpNAC6 from L. pumilum by observing phenotypic and physiological changes under stresses induced by salt, alkali, and drought. Furthermore, overexpression of LpNAC6 resulted in enhanced stress tolerance as evidenced by increased levels of SOD, POD, CAT enzymes, improved photosynthetic indices, and elevated chlorophyll contents; as well as reduced levels of MDA and reactive oxygen species (ROS). These findings demonstrate that we have successfully established a transgenic transformation method for L. pumilum while also providing essential information for cultivating stress-tolerant Lilium species and advancing our understanding of the functions of LpNAC6 in plants.

It Takes Two to Make a Thing Go Right: Epistasis, Two-Component Response Systems, and Bacterial Adaptation

Understanding the interplay between genotype and fitness is a core question in evolutionary biology. Here, we address this challenge in the context of microbial adaptation to environmental stressors. This study explores the role of epistasis in bacterial adaptation by examining genetic and phenotypic changes in silver-adapted Escherichia coli populations, focusing on the role of beneficial mutations in two-component response systems (TCRS). To do this, we measured 24-hour growth assays and conducted whole-genome DNA and RNA sequencing on E. coli mutants that confer resistance to ionic silver. We showed recently that the R15L cusS mutation is central to silver resistance, primarily through upregulation of the cus efflux system. However, here we show that this mutation’s effectiveness is significantly enhanced by epistatic interactions with additional mutations in regulatory genes such as ompR, rho, and fur. These interactions reconfigure global stress response networks, resulting in robust and varied resistance strategies across different populations. This study underscores the critical role of epistasis in bacterial adaptation, illustrating how interactions between multiple mutations and how genetic backgrounds shape the resistance phenotypes of E. coli populations. This work also allowed for refinement of our model describing the role TCRS genes play in bacterial adaptation by now emphasizing that adaptation to environmental stressors is a complex, context-dependent process, driven by the dynamic interplay between genetic and environmental factors. These findings have broader implications for understanding microbial evolution and developing strategies to combat antimicrobial resistance.

Phenotypic Change of Utilization Behavior Due to Reduction of Instinctive Grasp Reaction in a Case with a Right Medial Prefrontal Infarction : Factors Related to the Expression of Utilization Behavior and Its Phenotype

Phenotypic Change of Utilization Behavior Due to Reduction of Instinctive Grasp Reaction in a Case with a Right Medial Prefrontal Infarction : Factors Related to the Expression of Utilization Behavior and Its Phenotype

Neoadjuvant chemotherapy induces phenotypic mast cell changes in high grade serous ovarian cancer

BackgroundHigh grade serous ovarian cancer (HGSOC) is the most lethal gynecologic malignancy in which patients have still yet to respond meaningfully to clinically available immunotherapies. Hence, novel immune targets are urgently needed. Our past work has identified that mast cells are significantly upregulated at the mRNA level in HGSOC patient tumors following neoadjuvant chemotherapy (NACT) exposure. Therefore, in this current investigation we sought to characterize intratumoral mast cell phenotypic changes as a result of NACT exposure and determine how these adaptations are associated with patient clinical outcomes.MethodsHematologic immunohistochemistry was employed to determine mast cell levels in 36 matched pre- and post-NACT HGSOC patient tumors. Fluorescent Immunohistochemistry was utilized to identify Tryptase+(carboxypeptidase A3 (CPA3) + mast cells as well as histamine levels in 29 and 20, respectively, matched pre- and post-NACT HGSOC patient tumors. Finally, human immortalized mast cells, LUVA were stimulated with carboplatin and paclitaxel and genomic changes were analyzed by quantitative PCR.ResultsHematologic labeled intratumoral mast cells were significantly upregulated in the intraepithelial and stromal regions of the tumor, post-NACT. Lower levels of pre-NACT mast cells were significantly associated with an improved progression-free survival (PFS). Histamine, a marker of mast cell degranulation was similarly upregulated in post-NACT exposed tumors. Through the characterization of mast cell specific proteases Tryptase and CPA3, it was found that Tryptase+/ CPA3 + mast cells were significantly upregulated both in the intraepithelial and stromal compartments of the tumor, while Tryptase + cells were significantly upregulated in the stromal regions of the tumor. Lower post-NACT treated levels with Tryptase+/ CPA3 + cells were significantly associated with improved overall survival (OS) and PFS while higher Tryptase + mast cells were associated with improved OS. Finally, following chemotherapy exposure mast cell activating factors AREG and CCL2 were significantly upregulated while TGFB1, an inhibitor of mast cell activation was downregulated in LUVA cells.ConclusionsEnhanced mast cell numbers, as well as activation and degranulation are a consequence of NACT exposure. Post-NACT mast cells displayed differing associations with survival outcomes that was dependent upon granule classification. Ultimately, mast cells represent a clinically relevant putative HGSOC immune target.

Comparative analysis of changes in immune cell in the chicken spleen across different ages using flow cytometry

BackgroundConcurrent emerging and reemerging avian infectious diseases cause multiple risk factors in poultry. A body amount studies attempted to understand pathogen-associated immunity in chickens. Recent research has made progress in identifying immune functions in chicken, there are still gaps in knowledge, especially regarding immune responses during infectious diseases. A deeper understanding in chicken immune system is critical for improving disease control strategies and vaccine development.ResultsThis study proposes analytical method for chicken splenocytes, enabling the tracking changes in T cells, monocytes, and B cells across three ages. Optimized lymphocyte-activating conditions were suggested using concanavalin A and chicken interleikin-2, which facilitate immune cell activation and proliferation. Next, splenocytes from embryonic day 18, day 5, and day 30 were compared using surface markers and flow cytometry analysis. We observed an increase in T cell subsets, including activated T cells (CD4+CD44+ and CD8+CD44+), and B cells, along with a reduced monocyte population after hatching. However, morphological changes and genetic expression of functional immune molecules were limited.ConclusionsThe present findings on chicken immune system development offer valuable insights into the avian immune system, including analytical methods and the phenotypic and functional changes in immune cells. Updated immune-boosting strategies during the early stages of life are crucial for developing preventive measures against major infectious diseases in the poultry industry.

Evaluation of the impact of customized serum-free culture medium on the production of clinical-grade human umbilical cord mesenchymal stem cells: insights for future clinical applications

BackgroundThe selection of suitable culture medium is critical for achieving good clinical outcomes in cell therapy. To support the commercial application of stem cell therapy, customized culture media not only need to promote stem cell proliferation, but also need to save costs and meet industrial requirements for inter-batch consistency, efficacy, and biosafety. In this study, we developed a series of serum-free media (SFM) and elucidated the effects between different SFM, as well as between SFM and serum-containing meida (SCM), on human umbilical cord mesenchymal stem cells (hUC-MSCs) phenotype and function. We analyze and emphasize from the perspectives of clinical and commercial application why research on customized culture media is critical for the success of enterprises developing novel cellular therapeutics.MethodsWe cultured hUC-MSCs with identical cell seeding densities in different formulations of SFM and SCM until passage 10 and examined the changes in cell phenotype and function. We analyzed the results with the commercial application requirments of the cellular therapy industry to assess the potential impact of customized culture media on inter-batch consistency, efficacy, stability, biosafety, and cost-effectiveness of industrial-scale cell production.ResultshUC-MSCs cultured in SCM and SFM exhibit consistent cell morphology and surface molecule expression, but hUC-MSCs cultured in SFM demonstrate higher activity, superior proliferative capacity, and greater stability. Furthermore, hUC-MSCs cultured in different SFM exhibit differences in cell activity, proliferative capacity, senescent rate, and S/M ratio of cell cycle, while maintaining a normal karyotype after long-term in vitro cultivation. Moreover, we found that hUC-MSCs cultured in different media exhibit variations in paracrine capacity and in their support of hematopoietic stem cell (HSC) self-renewal.ConclusionConsidering the substantial funding and time required for cell-based drug development, our results underscore the importances of comprehensively optimizing the composition of medium for the specific disease prior to conducting clinical trials of cell-based therapies. The criteria for selecting culture medium should be based on the requirements of the target disease for cellular function. In addition, we provide a way to formulate different customized SFM, which is beneficial for the development of cell therapy industry.

Drug-induced change in transmitter identity is a shared mechanism generating cognitive deficits

Cognitive deficits are long-lasting consequences of drug use, yet the convergent mechanism by which classes of drugs with different pharmacological properties cause similar deficits is unclear. We find that both phencyclidine and methamphetamine, despite differing in their targets in the brain, cause the same glutamatergic neurons in the medial prefrontal cortex of male mice to gain a GABAergic phenotype and decrease expression of their glutamatergic phenotype. Suppressing drug-induced gain of GABA with RNA-interference prevents appearance of memory deficits. Stimulation of dopaminergic neurons in the ventral tegmental area is necessary and sufficient to produce this gain of GABA. Drug-induced prefrontal hyperactivity drives this change in transmitter identity. Returning prefrontal activity to baseline, chemogenetically or with clozapine, reverses the change in transmitter phenotype and rescues the associated memory deficits. This work reveals a shared and reversible mechanism that regulates the appearance of cognitive deficits upon exposure to different drugs.

A living organoid biobank of patients with Crohn’s disease reveals molecular subtypes for personalized therapeutics

Crohn's disease (CD) is a complex and heterogeneous condition with no perfect preclinical model or cure. To address this, we explore adult stem cell-derived organoids that retain their tissue identity and disease-driving traits. We prospectively create a biobank of CD patient-derived organoid cultures (PDOs) from colonic biopsies of 53 subjects across all clinical subtypes and healthy subjects. Gene expression analyses enabled benchmarking of PDOs as tools for modeling the colonic epithelium in active disease and identified two major molecular subtypes: immune-deficient infectious CD (IDICD) and stress and senescence-induced fibrostenotic CD (S2FCD). Each subtype shows internal consistency in the transcriptome, genome, and phenome. The spectrum of morphometric, phenotypic, and functional changes within the "living biobank" reveals distinct differences between the molecular subtypes. Drug screens reverse subtype-specific phenotypes, suggesting phenotyped-genotyped CD PDOs can bridge basic biology and patient trials by enabling preclinical phase "0" human trials for personalized therapeutics.

Phenotypic changes and gene expression profiles of Vibrio parahaemolyticus in response to low concentrations of ampicillin.

Vibrio parahaemolyticus is a leading cause of seafood-associated gastroenteritis and possesses intrinsic resistance to ampicillin. While ampicillin can trigger transcriptional responses of global genes, the behavioral and molecular changes that occur in V. parahaemolyticus when exposed to ampicillin are not fully understood. In this work, we investigated the effects of low concentrations of ampicillin on the physiology and gene expression of V. parahaemolyticus by combining phenotypic assays and RNA sequencing (RNA-seq) analysis. Our results showed that the growth of V. parahaemolyticus were notably delayed, and both motility and c-di-GMP production were significantly inhibited in the response to low concentrations of ampicillin stress. In contrast, biofilm formation by V. parahaemolyticus was enhanced by exposure to low concentrations of ampicillin. However, low concentrations of ampicillin had no effect on the cytotoxicity or adherence activity of V. parahaemolyticus. The RNA-seq data revealed that a low concentration of ampicillin significantly affected the expression levels of 676 genes, including those involved in antibiotic resistance, virulence, biofilm formation, and regulation. This work contributes to our understanding of how V. parahaemolyticus alters its behavior and gene expression in response to ampicillin exposure.

Gut Microbiota Dynamics and Phenotypic Changes Induced by Tetracycline in Drosophila melanogaster

Gut microbiota plays a crucial role in both physiological and pathological processes in humans and animals. Antibiotics, designed to combat bacterial infections, can induce alterations in the composition and abundance of the gut microbiota over prolonged exposure. This study addresses the limited understanding of the connections between gut microbiota and phenotypic profiles of metazoan species. We investigated the impact of early-life exposure to tetracycline in wild-type D. melanogaster, which were fed a standard diet, comparing them to a control group not exposed to tetracycline. The primary objective was to examine the consequences of early-life tetracycline exposure on gut microbiota and its implications for phenotypic profiles, including survival, locomotor activity, and reproduction in adult flies. Results revealed a significant reduction in lactic acid bacteria in adult flies exposed to tetracycline. However, tetracycline exhibited no interference with fly development, allowing them to maintain a normal lifespan. In adult flies, tetracycline significantly decreased the lifespan on day 35 at a concentration of 1000 µg/mL and reduced locomotion on day 27 at concentrations of 10 µg/mL and 1000 µg/mL. Remarkably, tetracycline did not impact the reproductive capabilities of the flies. This study demonstrates that while tetracycline led to a decline in lactic acid bacteria, locomotion, and lifespan in adult flies, it did not disrupt their development or reproductive processes.

Macrophage and chondrocyte phenotypes in inflammation.

Inflammation is a complex biological process protecting the body from diverse external threats. Effectively performing this task requires an intricate, well-regulated interplay of different cells and tissues. Furthermore, several cells participating in inflammation can assume diverse phenotypes. A classic and relatively well-studied example of phenotypic diversity in inflammation is macrophage polarization. Based on the TH1/TH2 phenotypes of T helper cells, this scheme has proinflammatory "classical/M1" activation contrasted with the anti-inflammatory and healing-promoting "alternative/M2" phenotype. Some authors have extended the concept into an M17 phenotype induced by the classic TH17 cytokine IL-17. Phenotypic changes in chondrocytes have also been studied especially in the context of osteoarthritis (OA), and there are indications that these cells can also assume polarized phenotypes at least partly analogous to those of TH cells and macrophages. The therapeutic success of biological agents targeting TH1/TH2/TH17 inductor and/or effector cytokines displays the utility of the concept of polarization. The aim of this focused review is to survey the internal and external factors affecting macrophage and chondrocyte phenotypes (such as inflammatory cytokines, widely used medications and natural products) and to explore the possibility of ameliorating pathological states by modulating these phenotypes.